The present invention relates to novel compositions of matter. The present invention also relates to a new use for some old compounds. More particularly, the present invention relates to certain aminoalkyl or aminoalkenyl triazoles which are useful as anti-psychotic agents. Some of these compounds are also useful as analgesics.
Anti-psychotic or neuroleptic drugs are those used to treat the most severe psychiatric illnesses, the psychoses. The psychoses are a class of psychiatric diseases in which there is not only a marked impairment of an individuals behavior but also a serious inability of those afflicted to think coherently, to comprehend reality, or to gain insight into their own abnormality. These conditions often include delusions and hallucinations. Psychotic disorders include organic conditions which are typically associated with toxic, metabolic, or neuropathologic changes and are characterized by confusion, disorientation, and memory disturbances as well as behavioral disorganization and idiopathic (or functional) disorders for which underlying causes remain completely obscure. These latter disorders are characterized by the retention of orientation and memory in the presence of severely disordered emotion, thought, and behavior. Those primary disorders characterized by abnormal emotion or mood are called manic depressive disorders. The class of idiopathic psychoses characterized mainly by disordered thinking and emotional withdrawal, and often associated with paranoid delusions and auditory hallucinations, are called schizophrenia. The psychoses can vary in severity and they present a variety of specific symptom clusters. In addition, there are disorders marked by more or less isolated delusions. These latter disorders are sometimes referred to in a separate category of illness called paranoia. For a general discussion of psychoses, see, e.g., Goodman and Gilman, The Pharmacological Basis of Therapeutics, 391 (1980).
Several classes of drugs have been used for symptomatic treatment of psychoses. They are most often used in the treatment of schizophrenia, organic psychoses, and the manic phase of manic depressive illness. These classes of drugs include compounds such as the phenothiazines, the thioxanthenes, the dibenzodiazepines and dibenzoxazepines, the butyrophenones, the diphenylbutylpiperidines, the indolones and other heterocyclic compounds, and the rauwolfia alkaloids and related synthetic heterocyclic amine-depleting agents. Chlorpromazine is commonly used as a prototype for the group of anti-psychotic drugs. The chemical name for this compound is 2-chloro-N,N-dimethyl-10H-phenothiazine-10-propanamine. Many anti-psychotic drugs have sedative effects, as well as anti-anxiety effects. However, these antipsychotic compounds are not generally used for such purposes, because of their neurological and autonomic side effects. The term neuroleptic is used to define this class of drugs based on the observation of the effects of these drugs in humans. These drugs suppress spontaneous movements and complex behavior, while spinal reflexes and unconditioned nociceptive-avoidance behaviors remain intact. In humans, these drugs cause a striking loss of initiative, disinterest in the environment, diminished emotional responsiveness and limited range of affect. While initially there might be some slowness in response to external stimuli and drowsiness, subjects are generally easily aroused, capable of giving appropriate answers to direct questions, and seem to have their intellectual function intact. There is no ataxia, incoordination, or dysarthria. For a discussion of antipsychotic drugs which are currently used, see Goodman and Gilman, supra, at 397.
While the use of anti-psychotic or neuroleptic drugs has achieved some success, there is a need for an anti-psychotic drug which lacks the catalepsy and muscle rigidity or extra pyramidal side effects seen in humans given typical neuroleptics and which does not produce the late onset dyskinesia typically observed in patients chronically treated with neuroleptics.